RT Journal Article
T1 Multiplexed biosensing diagnostic platforms detecting autoantibodies to tumor-associated antigens from exosomes released by CRC cells and tissue samples showed high diagnostic ability for colorectal cancer
A1 Montero Calle, Ana
A1 Aranguren Abeigon, Itziar
A1 Garranzo Asensio, María
A1 Povés Francés, Carmen
A1 Fernández Aceñero, María Jesús
A1 Martínez Useros, Javier
A1 Sanz López, Rodrigo
A1 Dziakova, Jana
A1 Rodríguez Cobos, Javier
A1 Solís Fernández, Guillermo
A1 Povedano, Eloy
A1 Gamella Carballo, María
A1 Torrente Rodríguez, Rebeca Magnolia
A1 Alonso Navarro, Miren
A1 Ríos, Vivian de los
A1 Casal, J. Ignacio
A1 Domínguez Muñóz, Gemma
A1 Guzmán Aránguez, Ana Isabel
A1 Peláez García, Alberto, Alberto
A1 Pingarrón Carrazón, José Manuel
A1 Campuzano Ruiz, Susana
A1 Barderas Manchado, Rodrigo
AB Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The 5-year survival rate of CRC patients depends on the stage at diagnosis, being higher than 80% when CRC is diagnosed in the early stages but lower than 10% when CRC is diagnosed in advanced stages. Autoantibodies against specific CRC autoantigens (tumor-associated antigens (TAAs)) in the sera of patients have been widely demonstrated to aid in early diagnosis. Thus, we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.  To  that  end,  we  examined  the  protein  content  of the exosomes  released  by  five  CRC  cell  lines  and  tissue  samples  from  CRC  patients  by means  of immunoprecipitation coupled with mass spectrometry analysis. A total of 103 proteins were identified as potential autoantigens specific to CRC. After bioinformatics and meta-analysis, we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot (WB) and immunohistochemistry (IHC). We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients, along with an association of nine of these proteins with CRC prognosis. After validation, all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals, either by luminescence Halotag-based beads, or by a multiplexed biosensing platform involving  the  use  of  magnetic  microcarriers  as  solid  support  modified  with  covalently  immobilized  Halotag  fusion  proteins  constructed  for  CRC  detection. Taken together, our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases; they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care (POC) device for CRC detection with high diagnostic ability.
PB Elsevier
SN 2095-8099; 2096-0026 (e)
YR 2021
FD 2021-08-14
LK https://hdl.handle.net/20.500.14352/4416
UL https://hdl.handle.net/20.500.14352/4416
LA eng
NO Received: 30 September 2020 / Revised: 5 February 2021 / Accepted: 27 April 2021 / Available online: 14 August 2021.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
NO Ministerio de Ciencia e Innovación (MICINN)
NO Instituto de Salud Carlos III (ISCIII)
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (MINECO)
NO FIS and Cátedra UAM-Roche en Medicina de Innovación
NO Comunidad de Madrid
DS Docta Complutense
RD 8 abr 2025